Diols, desymmetrization meso. oxidation

Subsequent to the development of the (salen)Cr-catalyzed desymmetrization of meso-epoxides with azide (Scheme 7.3), Jacobsen discovered that the analogous (salen)Co(n) complex 6 promoted the enantioselective addition of benzoic acids to meso-epoxides to afford valuable monoprotected C2-symmetric diols (Scheme 7.15) [26], Under the reaction conditions, complex 6 served as a precatalyst for the (salen) Co(iii)-OBz complex, which was fonned in situ by aerobic oxidation. While the enantioselectivity was moderate for certain substrates, the high crystallinity of the products allowed access to enantiopure materials by simple recrystallization. 

With a good route to the key meso diol 128 in hand, the authors turned their attention to desymmetrization, using the known asymmetric hydrolysis of meso diacetates by Lipase AK (Scheme 23). The meso diol 128 was first converted to diacetate 140, and then hydrolyzed with Lipase AK to cleave selectively one of the two acetates, producing chiral hydroxyester 141. Oxidation, cleavage of the acetate, and lactonization yielded the (3S,4.R) lactone 129. The corresponding lactol (3S,4 )-130 was found to be the enantiomer of the compound produced in the HLADH synthesis. 

Catalytic oxidation is a possible means of kinetic resolution of racemic mixtures of alcohols (Scheme 10.19, Eq. 1) or of desymmetrization of meso-diols (Scheme 10.19, Eq. 2). 

A series of meso-dihydrobenzoins was also subjected to oxidative desymmetrization. Three equivalents of the chiral ketone 88 again provided the chiral dioxirane as the active species [138, 139]. As shown in Table 10.14, enantiomeric excesses up to 60% were achieved. In addition to the meso diols themselves, acetonides also proved suitable substrates in two instances (Table 10.14). 

The desymmetrization of meso diols requires selective chemical transformation of one of the two enantiotopic hydroxyl functions. Among other possibilities this transformation can consist in acylation or - less commonly - oxidation to a ketone (Scheme 13.19). It should be noted that the enantiomeric purity of the initial reaction products can be upgraded by subsequent conversion of the unwanted enantiomer into the diacylated compound (or diketone), i.e. by subsequent kinetic resolution. 

As a rule of thumb, oxidation of the (S)- or pro-(S ) hydroxyl group occurs selectively with HLADH (Scheme 2.143). In the case of 1,4- and 1,5-diols, the intermediate y- and 8-hydroxyaldehydes spontaneously cyclize to form the more stable five- and six-membered hemiacetals (lactols). The latter are further oxidized in a subsequent step by HLADH to form y- or 5-lactones following the same (S)-or pro-(5) specificity [1035]. Both steps - desymmetrization of the prochiral or meso-diol and kinetic resolution of the intermediate lactol - are often highly selective. By using this technique, enantiopure lactones were derived from... 

Shimizu, H., Onitsuka, S., Egami, H., et al. (2005). Ruthenium(Salen)-Catalyzed Aerobic Oxidative Desymmetrization of Meso-Diols and its Kinetics, J. Am. Chem. Soc., 127, pp. 5396-5413. 

Aerobic Alcohol Oxidations. The combination of PdCl2(CH3CN)2 (5-10 mol%) with (—(-sparteine (20 mol%) constitutes an effective catalyst system for the oxidative kinetic resolution of secondary alcohols with molecular oxygen as the terminal oxidant, with enantiomeric excesses t)q)ically above 90% ee (eq 45). This enantioselective aerobic oxidation has been successfully extended to the desymmetrization of meso-1,3-diols. 

Other examples include OKR of racemic secondary alcohols (Scheme 25A), oxidative desymmetrizations of meso-diols, etc. The kinetic resolution is generally defined as a process where two enantiomers of a racemic mixture are transformed to products at different rates. Thus, one of the enantiomers of the racemate is selectively transformed to product, whereas the other is left behind. This method allows to reach a maximum of 50% yield of the enantiopure remaining sec-alcohol. To overcome this fim-itation, a modification of the method, namely dynamic kinetic resolution (DKR), was introduced. In this case, the kinetic resolution method is combined with a racemization process, where enantiomers are interconverted while one of them is consumed (e.g., by esterification. Scheme 25B). Therefore, a 100% theoretical yield of one enantiomer can be reached due to the constant equifibrium shift. In most of the proposed DKR processes, several catalytic systems, e.g., enzymes and transition-metal catalysts, work together. Both reactions (transfer hydrogenation of ketones and the reverse oxidation of secondary alcohols using ketone as a hydrogen acceptor) can be promoted by a catalyst. The process can involve a temporary oxidation of a substrate with hydrogen transfer to a transition-metal complex. 

Suzuki T, Morita K, Matsuo Y, Hiroi K. Catalytic asymmetric oxidative lactonizations of meso-diols using a chiral iridium complex. Tetrahedron Lett. 2003 44 2003—2006. Moritani J, Hasegawa Y, Kayaki Y, Ikariya T. Aerobic oxidative desymmetrization of meso-diols with bifunctional amidoiridium catalysts bearing chiral N-sulfonyldiamine ligands. Tetrahedron Lett. 2014 55 1188-1191. 

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